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DOI: 10.1055/s-2003-43371
Synthesis of 2-Monosubstituted Pyrroles by Intramolecular Addition of Amines via Reductive Amination with Dibutyliodotin Hydride Complex (Bu2SnIH-HMPA)
Publikationsverlauf
Publikationsdatum:
04. Dezember 2003 (online)
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Abstract
Various 2-monosubstituted pyrroles were prepared in a one-pot procedure via the reductive amination of formyl groups of multifunctional substrates 1 by using Bu2SnIH-HMPA system.
Key words
pyrroles - reductive amination - tin hydride - complex
- 1
Shibata I.Moriuchi-Kawakami T.Tanizawa D.Suwa T.Sugiyama E.Matsuda H.Baba A. J. Org. Chem. 1998, 63: 383 - 2
Suwa T.Sugiyama E.Shibata I.Baba A. Synlett 2000, 556 - 3 For most recent work, see:
Lee C.-F.Yang L.-M.Hwu T.-Y.Feng A.-S.Tseng J.-C.Luh T.-Y. J. Am. Chem. Soc. 2000, 122: 4992 ; and references therein - For a review see:
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4a
Gossauer A. In Pyrrole, Houben-Weyl, Methods in Organic Chemistry Vol. E6a/1: Thieme; Stuttgart: 1994. p.556 -
4b See also:
Boger DL.Boyce CW.Labroli MA.Sehon CA.Jin Q. J. Am. Chem. Soc. 1999, 121: 54 -
4c
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4e
Liu J.-H.Yang Q.-C.Mak TCW.Wong HNC. J. Org. Chem. 2000, 65: 3587 - For formation of the 2-monosubstituted pyrrole ring from γ-keto aldehydes or related precursors, see:
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5a
Ref. [4a]
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Gadzhily RA.Fedoseev VM.Dzhafarov VG. Chem. Heterocycl. Compd. 1990, 26: 874 -
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5d For syntheses of 2-monosubstituted pyrroles via acylation-reduction or alkylation of pyrrole see, for example:
Garrido DOA.Buldain G.Frydman B. J. Org. Chem. 1984, 49: 2619 -
5e
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5f See also:
Kel’in AV.Sromek AW.Gevorgyan V. J. Am. Chem. Soc. 2001, 123: 2074 - 6 For preparation of 1, see:
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Kawakami T.Shibata I.Baba A. J. Org. Chem. 1996, 61: 82 - We have already reported the increase of nucleophilicity of Sn-N bonds by pentacoordination, see:
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References
Typical Experimental Procedure (see Table
[1]
, entry 3).
To a dry nitrogen-filled 10 mL round-bottomed flask containing di-n-butyltin dihydride (Bu2SnH2, 0.166 g, 0.5 mmol) in 1,4-dioxane (1 mL) was added di-n-butyltin diiodide (Bu2SnI2, 0.243 g, 0.5 mmol) and HMPA (0.180 g, 1 mmol) at r.t. After stirring at r.t. for 10 min, the resulting solution of di-n-butyliodotin hydride (Bu2SnIH, 1 mmol) was cooled to 0 °C. Carbonyl substrate(1a) (0.196 g, 1 mmol), and p-chloroaniline (0.128 g) were added successively, and stirring was continued at 0 ºC for 2 h. The IR absorption band of Sn-H (1850 cm-1) disappeared, which indicated the formation of stannylamide (II). The mixture was heated to 80 ºC and stirred for 2 h. The reaction was quenched with MeOH (0.5 mL), and the residue was chromatographed on silica-gel column [FL100-DX (Fuji silysia)]. Elution with hexane gave pyrrole 2a (0.234 g, 81%).
Spectral data of representative products are as follows.
Compound 2a. IR: 1596, 1496 cm-1. 1H NMR (CDCl3): δ = 0.86 (t, J = 6.83 Hz, 3 H), 1.21-1.30 (m, 10 H), 1.44-1.55 (m, 2 H), 2.49 (t, J = 7.81 Hz, 2 H), 6.04-6.06 (m, 1 H), 6.21 (t, J = 2.93 Hz, 1 H), 6.67-6.69 (m, 1 H), 7.22 (d, J = 8.79 Hz, 2 H), 7.39 (d, J = 8.79 Hz, 2 H). 13C NMR (CDCl3): δ = 14.08, 22.63, 26.65, 29.13, 29.27, 29.30, 31.57, 31.80, 107.10, 108.26, 121.30, 127.30, 129.18, 132.77, 134.21, 139.06. HRMS: calcd for C18H24NCl: 289.1597. Found: 289.1597.
Compound 2e. IR: 1496 cm-1. 1H NMR (CDCl3): δ = 1.75-1.87 (m, 2 H), 2.51-2.59 (m, 4 H), 6.06-6.09 (m, 1 H), 6.18-6.21 (m, 1 H), 6.66-6.68 (m, 1 H), 7.05-7.35 (m, 9 H). 13C NMR (CDCl3): δ = 26.09, 30.67, 35.29, 107.39, 108.32, 121.46, 125.71, 127.19, 128.25, 128.31, 129.20, 132.76, 133.49, 138.87, 141.86. HRMS: calcd for C19H18NCl: 295.1128. Found: 295.1125.
Compound 2f. IR: 1600, 1492 cm-1. 1H NMR (CDCl3): δ = 6.35-6.38 (m, 1 H), 6.42-6.44 (m, 1 H), 6.90-6.91 (m, 1 H), 7.09 (d, J = 8.40 Hz, 2 H), 7.13-7.24 (m, 5 H), 7.28 (d, J = 8.40 Hz, 2 H). 13C NMR (CDCl3): δ = 109.60, 110.99, 124.16, 126.49, 126.76, 128.18, 128.32, 129.13, 132.19, 132.59, 133.79, 139.01. HRMS: calcd for C16H12NCl: 253.0658. Found: 253.0653.
It seems that chlorodibutyltin amide moiety (Bu2ClSnN-) does not has enough nucleophilicity to cause cyclization because of the electron withdrawing character of Cl-substituent (entry 4).